The mu opioid receptor (MOR) is akey mediator of the analgesic and rewarding/addictive properties of opiate drugs. All opioid receptors are members of surperfamily of 7 transmembrance-domain G-protein coucled receptors. Opioid ligands generally have inhibitory effects on sunaptic transmission. However, MOR is thought to be able to interact with numerous G-protein alpha subunits. The goal of this proposal is to gain insight into the vivo interactions between MOR and G-protein alpha subunits. Since bith MOR and G-protein alpha subunits demonstrate a selective cellular and subcellular localization, I propose an anatomical apprach to detemine if their is regional, cellular, and subcellular specilicity in the colocalization between NOR and G-protein. In addition a complimentary biochemical apprach will more directly address weather colocailization represents a functional interaction. Furthermore, since opiate signaling pathways are modified with the development of toloerance and dependence, I propose tp determine if the relationships I observe bewteen MOR and G-proteins change with chronic opiate drug treatment.